CuFe2O4@SiO2@L-arginine@Cu(I) as a new magnetically retrievable heterogeneous nanocatalyst with high efficiency for 1,4-disubstituted 1,2,3-triazoles synthesis

A novel magnetic heterogeneous catalyst was synthesized through the immobilization of copper ions onto the l-arginine functionalized CuFe2O4@SiO2. The prepared catalyst was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), and Energy Dispersive X-Ray spectroscopy (EDX). The resulting catalyst was used in the ultrasonic-assisted synthesis of 1,2,3-triazoles via a one-pot three-component reaction of alkynes, alkyl halides, and sodium azides under green conditions within a short time. The catalyst reusability was investigated after five cycles and no significant loss of activity was observed.

www.nature.com/scientificreports/ But the major disadvantages associated with these homogeneous copper catalysts are the difficulties to recover and reuse for successive reaction cycles and the possibility of metal contamination with the end product. To overcome these serious issues, various solid-supports like zeolites [53], polymers [54,55], carbon [44], silica [56] etc. have been employed to synthesize the corresponding heterogeneous copper catalysts by immobilizing the active metal ions onto the solid supports.
In continuation of our work on the synthesis of heterocyclic structures [22][23][24] , we reported the synthesis of a new efficient magnetite-base catalytic system, CuFe 2 O 4 @SiO 2 @l-arginine@Cu, along with its application in an approach to 1,2,3-triazole derivatives. The procedure uses phenylacetylene as an alkyne, sodium azide, and various alkyl halides as the other component to form triazoles. The reaction was done in ultrasonic-assisted green conditions and the catalyst removed with an external magnet (Fig. 1). The reaction yields were excellent and the prepared catalyst has a good efficiency even after five cycles.

Experimental section
Materials. All the reactants were purchased from Merck Chemical Company and Aldrich and used without further purification. Fourier transform infrared (FT-IR) spectra were recorded as KBr pellets using a Bruker VRTEX 70 model FT-IR spectrophotometer. Powder X-ray diffraction (XRD) patterns were collected with a Rigaku-Dmax 2500 diffractometer with nickel filtered Cu Kα radiation (λ = 1.5418 Å, 40 kV). Supermagnetic properties of the catalyst were measured with a vibrating sample magnetometer at room temperature.
Preparation of CuFe2O4@SiO2 nanoparticles. CuFe 2 O 4 was readily synthesized using a chemical co-precipitation method previously reported 25 , followed by a SiO 2 -coating procedure 26 . Briefly, 2.00 g of the obtained CuFe 2 O 4 was dispersed in a mixture of 100 mL of ethanol, 40 mL of deionized water and 6 mL of concentrated aqueous ammonia solution, followed by the addition of 4 mL tetraethylorthosilicate (TEOS). This solution was stirred mechanically at room temperature overnight. Then the product, CuFe 2 O 4 @SiO 2 , was separated using an external magnet, washed with deionized water and ethanol three times, and dried at room temperature.

Preparation of CuFe2O4@SiO2@l-arginine@Cu(I).
In the second step, CuFe 2 O 4 @SiO 2 @l-arginine nanocatalyst was synthesized using the following procedure. An amount of 1 g of CuFe 2 O 4 @SiO 2 was suspended in deionized water (20 mL) and became highly dispersed via sonication. Then, 2 g of l-arginine was added and the mixture was stirred at 90 °C for 15 h. CuFe 2 O 4 @SiO 2 @l-arginine nanoparticles were separated from the aqueous solution by applying an external magnet, washed with distilled water and then dried in an oven. The whole synthesis was done under an inert atmosphere. In the last step, incorporation of copper onto the CuFe 2 O 4 @SiO 2 @l-arginine nanocomposite was carried out by mixing the CuFe 2 O 4 @SiO 2 @l-arginine (1 g) and CuI (0.5 g) in absolute ethanol (50 mL). The mixture was refluxed for 24 h. Cu(I) ions were adsorbed onto the magnetic nanocarrier. Finally, the synthesized CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) nanocomposite as a brown powder was separated from the suspension using magnetic decantation, washed with absolute ethanol and dried under vacuum at room temperature.
General procedure for preparation of triazoles. A mixture of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) (1 mol% of Cu), benzyl halide (1.0 mmol), phenylacetylene derivatives (1.2 mmol), and NaN 3 (1.2 mmol) in a 1:1 mixture of H 2 O:EtOH (3 ml) was irradiated under sonication for an appropriate time (Tables S1 and S2). After completion of the reaction monitored by TLC, the catalyst was separated with an external magnet and the solvents were removed under vacuum evaporator and the product was further purified by EtOH/water system.

Results and discussion
The synthetic pathway of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) is illustrated in Fig. 2. CuFe 2 O 4 NPs were prepared through a co-precipitation method by dissolving salts into distilled water, followed by precipitation with NH 4 OH. Afterward, TEOS was hydrolyzed to form silica oligomers, which were coated on the surface of CuFe 2 O 4 nanoparticles to obtain CuFe 2 O 4 @SiO 2 nanoparticles. CuFe 2 O 4 @SiO2@l-arginine was obtained by nucleophilic addition of arginine to as-prepared magnetic nanoparticles. Subsequently, the copper was linked to the nitrogen groups of arginine. The morphology and the structure of the CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) was characterized by SEM and TEM analysis ( Fig. 3a-f). The almost uniform distribution and spherical structure of the catalyst is clearly observable in SEM images. The core-shell structure of the magnetic particles was proofed via TEM analysis with the black centers and the brightest areas as CuFe 2 O 4 cores and SiO 2 shells, respectively.

Characterization of the
The Brunauer-Emmett-Teller (BET) method was applied to calculate the surface area and pore diameter of the prepared catalyst. According to the BET analysis results presented in Fig. S2 (See supporting information), the surface area and average pore diameter are 33.65 m 2 /g and 17.59 nm for CuFe 2 O 4 @SiO 2 @L-arginine@Cu(I) catalyst.
To determine the oxidation states of Cu in the prepared catalyst, XPS analysis was performed. The XPS analysis of the CuFe 2 O 4 @SiO 2 @L-arginine@Cu(I) nanoparticles (Fig. S3, supporting information) revealed the characteristics peaks for C 1 s (284.88), O 1 s (530.39), Fe 2p (710.89) and Cu 2p (933.01). The Cu2p3/2 peaks located at 933.0 eV was attribute to Cu 1 .
The EDS analysis results confirmed the presence of carbon, oxygen, nitrogen, copper, iron, and Si elements in the catalyst (ratios of 9.0: 27.6: 0.4: 6.4: 23.9: 32.8 wt%, respectively) shown in Fig. 4 and inset. It also confirms the immobilization of Cu on CuFe 2 O 4 @SiO 2 @l-arginine was achieved successfully. Moreover, the accurate amount of copper in the final catalyst composition determined via ICP analysis was 9.14%.
The magnetic properties of CuFe 2 O 4 , CuFe 2 O 4 @SiO 2 and CuFe 2 O 4 @SiO 2 @l-arginine@Cu (I) were studied using VSM analysis at ambient temperature with the magnetic field sweeping from − 10,000 to + 10,000 Oe, and the magnetization cycles are shown in Fig. S4 (see supporting information). Obviously, the particles showed zero remanent magnetization which is the reason for their superparamagnetic behavior. Superparamagnetic nanoparticles would not aggregate magnetically due to the lack of net magnetization in the absence of an external field 27 29 . The slightly broad diffraction peak at 2θ value 20-30° was attributed to the amorphous silica indicated the formation of SiO 2 shell does not change the crystal form of CuFe 2 O 4 (JCPDS card no.00-002-0278). The XRD pattern of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) revealed a sharp peak at 28.438 attributed to CuI. Moreover, the XRD pattern of reused CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) showed that the crystalline structure of catalyst remained unchanged after several runs. (The reference card numbers were collected from the X'pert HighScore Plus version 1.0d software developed by the PANalytical B.V.) Thermal behavior of the prepared catalyst was analyzed using TGA and DTG under Ar atmosphere at a temperature varying from 50 to 800 °C and the plotted curve shown in Fig. S6 (See supporting information). The TGA thermogram of CuFe 2 O 4 @SiO 2 @L-arginine@Cu(I) shows two stage weight loss over the temperature range of TG analysis. The first stage, including a low amount of weight loss (6%) at T ~ 110 °C, resulted from

Evaluation the catalytic activities of CuFe 2 O 4 @SiO 2 @l-arginine-Cu(I) in the synthesis of 1,2,3-triazole derivatives. The catalytic behavior of CuFe 2 O 4 @SiO 2 @l-arginine-Cu(I) was investigated
for the synthesis of triazole derivatives via a three-component reaction between sodium azide, phenylacetylene, and benzyl halide under different conditions. To find the optimal reaction conditions, various factors such as catalyst loading, solvent, time and reaction temperature were scrutinized in a model reaction including phenylacetylene, benzyl bromide, and sodium azide presented in Table S1 (see supporting information). For further optimization, the type of catalyst was also investigated and tabulated in Table S2 (See supporting information). The results revealed the high performance of CuFe 2 O 4 @SiO 2 @l-arginine-Cu(I) due to synergistic effects and improved number of active sites on the surface. The conversion of 87% was reached for 15 mg catalyst loading under ultrasonic irradiation. Obviously, the increase in catalyst loading was not favorable. On the other hand, with an amount of catalyst of 30 mg, the yield did not change significantly compared to 15 mg.
To generalize the optimum conditions, different 1,2,3-triazole derivatives from 4a-j were prepared through a one-pot reaction of acetylene derivatives 1, sodium azide 2 and benzyl halide derivatives in the presence of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) (Fig. 5). The results are summarized in Table 1. As expected, the presence of electron-withdrawing groups on benzyl halide can enhance the rate and yield of the reaction. On the other hand, the reaction with benzyl bromide is much better than benzyl chloride. It can perhaps be because of the fact that -Br is a good leaving group in the substation reaction of azide anion.
In addition, for better characterization of the products the 1 HNMR spectra of the samples 4 h and 4i have been represented in Figs. S8 and S9 respectively (see supporting information).  www.nature.com/scientificreports/ Additionally, the efficiency of the catalyst was shown via the turnover number (TON) and turnover frequency (TOF) of the catalyst and provided in Table 1. As can be seen, the obtained values of TOF are between 2 and 5.6 S -1 , which is very valid for relevant industrial applications, for which the TOF is in the range10 −2 and 10 2 S −130 .
The proposed mechanism of the model reaction for triazole derivatives synthesis is mentioned in Fig. 6. In the first step the bifunctional catalyst forms copper acetylide (A). On the other hand, the organic azide was synthesized in-situ by the reaction of aryl halide with NaN 3 . Then the coordination of the organic azide to the copper acetylide was occurred and by the Huisgen 1, 3-dipolar cycloaddition reaction of (A) and (B) the final desired 1,2,3 triazole (C) obtained.
Hot filtration. The hot filtration test was carried out to investigate the heterogeneous nature of the CuFe 2 O 4 @ SiO 2 @l-arginine@Cu(I) in the synthesis of 1,2,3 triazole. At first, the model reaction was performed under the optimized reaction condition. After 10 min (43% conversion), the catalyst was removed from the reaction by an external magnet and also simple filtration. The reaction was then allowed to proceed without catalyst for 30 min. The results showed that the reaction did not progress in the absence of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I), thus proving the heterogeneity of the catalyst and the non-leaching of copper in the solution.
Catalyst recyclability. The easy separation of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) as a heterogeneous catalyst was mentioned before. In this regard, the recyclability of the nanocatalyst in the model reaction was investigated. At the end of the reaction, CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) was collected by an external magnetic field and washed with ethanol and water. The dried magnetic nanocatalyst was successively used for five times in the model reaction with a yield of 75%. According to the results displayed in Fig. S7 (see supporting information), there is no significant reduction in the catalytic efficiency of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I). Furthermore, according to the FESEM images shown in Fig. 3c,d there is no structural changes in catalyst after 5 times recycling. FTIR spectra of the fresh and recycled catalyst were shown in Fig. S1 (see Supporting Information). It is clear that the used catalyst has not undergone any structural changes.
In order to determine the catalytic efficacy of the prepared CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) in the preparation of 1,2,3 triazoles, the present work was compared with the previous reports. As it is obvious, the prepared catalyst has several advantages in the time of reaction time, solvent, and yield which are presented in Table 2.

Conclusions
In summary, we devised a novel collagen-coated superparamagnetic organic-inorganic hybrid catalyst, CuFe 2 O 4 @ SiO 2 @l-arginine@Cu(I), which exhibited radically enhanced catalytic activity in the synthesis of a wide range of substituted 1,2,3 triazole derivatives through a one-pot atom economical Huisgen 1, 3-dipolar cycloaddition reaction of acetylene derivatives, sodium azide, and benzyl halide under ultrasonic irradiation. This heterogeneous catalyst efficiency is achieved in several aspects, such as high product yields and reactivity in a green manner, stability, recyclability, and high reaction rate. Furthermore, the easy separation and removal from the reaction make this catalyst a good choice for use in other synthetic applications. These results affirmed that the novel CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I) can be used as a versatile catalyst for promoting chemical reactions.  Figure 6. Proposed catalytic mechanism of CuFe 2 O 4 @SiO 2 @l-arginine@Cu(I).